Studies of patients with a variety of genetic diseases are conducted. The relationship between specific cytogenetic variations and their phenotypic expression is stressed. Certain apparent single gene disorders and diseases with possible multifactorial etiology have also been studied in order to determine if they are associated with primary or secondary chromosomal abnormalities. These conditions include anosmic hypogonadotropic hypogonadism, the fragile X syndrome, autism, Alzheimer's disease, Down syndrome, various specific chromosomal deletions or duplications, and certain congenital malformation syndromes. Techniques used following clinical assessment of patients and their families include high resolution chromosomal analysis utilizing a wide variety of differential staining methods, in vitro induction of the fragile X marker chromosome, and analysis of genetic markers such as enzymes or HLA within pedigrees. Chromosomal and other findings are correlated with phenotypic abnormalities, and the results utilized for genetic counseling. Related studies of mice with chromosome defects are carried out also, in order to determine effects of autosomal trisomy at the cellular level.